反应详情

To a solution of the compound of Step 1 (19.6 g, 63.2 mmol), diisopropylethylamine (16.5 g, 127 mmol), and CH2Cl2 (200 mL) was added trifluoromethanesulfonic anhydride (17.8 g, 63.2 mmol) via syringe pump at −60° C. over 30 minutes. The resulting solution was then warmed to −20° C. over 1.5 h, whereupon diisopropylethylamine (5.5 g, 42.5 mmol) was added followed by 3,3-difluoropiperidine hydrochloride (6.67 g, 42.5 mmol). The mixture was then slowly warmed to rt over 5 h. After 12 h at rt, the reaction was partitioned between H2O (150 mL) and CH2Cl2 (100 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (3×100 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated. The residue was purified on silica gel (1:99→99:1 ethyl acetate-hexanes) to afford the title compound as a colorless foam: 1H NMR (500 MHz, CDCl3) δ 8.16 (s, 1H), 8.10 (d, 1H), 7.88 (d, 1H), 7.68 (t, 1H), 4.48-4.59 (m, 1H), 3.73 (s, 3H), 3.68-3.65 (m, 1H), 3.22-3.17 (m, 2H), 2.64 (br q, 1H), 2.51 (br q, 1H), 2.42-2.41 (m, 2H), 2.23-2.20 (m, 1H), 2.13-2.04 (m, 1H), 1.90-1.82 (m, 2H), 1.74-1.72 (m, 2H); LRMS (ESI) m/z 414 (414 calcd for C18H21F2N3O4S, M+H).

1. additionwas added
2. customthe reaction was partitioned between H2O (150 mL) and CH2Cl2 (100 mL)
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with CH2Cl2 (3×100 mL)
5. dry with materialThe combined organic layers were dried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified on silica gel (1:99→99:1 ethyl acetate-hexanes)